Clinical Study Micro-Bypass Implantation for Primary Open ...downloads.hindawi.com/journals/joph/2015/795357.pdf · Purpose . To report the long-term follow-up results in patients

Clinical StudyMicro-Bypass Implantation for Primary Open-Angle GlaucomaCombined with Phacoemulsification: 4-Year Follow-Up

Antonio Maria Fea, Giulia Consolandi, Marta Zola, Giulia Pignata, Paola Cannizzo,Carlo Lavia, Teresa Rolle, and Federico Maria Grignolo

Ophthalmic Clinic, Department of Surgical Sciences, University of Turin, 10122 Turin, Italy

Correspondence should be addressed to Giulia Pignata; [email protected]

Received 2 September 2015; Accepted 7 October 2015

Academic Editor: Colin Clement

Copyright © 2015 Antonio Maria Fea et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Purpose. To report the long-term follow-up results in patients with cataract and primary open-angle glaucoma (POAG) randomlyassigned to cataract surgery combined with micro-bypass stent implantation or phacoemulsification alone. Methods. 36 subjectswith cataract and POAG were randomized in a 1 : 2 ratio to either iStent implantation and cataract surgery (combined group) orcataract surgery alone (control group). 24 subjects agreed to be evaluated again 48 months after surgery. Patients returned onemonth later for unmedicated washout assessment. Results. At the long-term follow-up visit we reported a mean IOP of 15,9 ±2,3mmHg in the iStent group and 17 ± 2,5mmHg in the control group (𝑝 = NS). After washout, a 14,2% between group differencein favour of the combined groupwas statistically significant (𝑝 = 0, 02) formean IOP reduction. A significant reduction in themeannumber of medications was observed in both groups compared to baseline values (𝑝 = 0, 005 in the combined group and 𝑝 = 0, 01in the control group). Conclusion. Patients in the combined group maintained low IOP levels after long-term follow-up. Cataractsurgery alone showed a loss of efficacy in controlling IOP over time. Both treatments reduced the number of ocular hypotensivemedications prescribed. This trial is registered with: NCT00847158.

1. Introduction

Primary open-angle glaucoma (POAG) accounts for at least90% of all glaucoma cases and affects primarily 3 millionpeople in the United States. Cedrone et al. reported a 3,2%incidence of POAG in the population-based Ponza eye study[1]. Increased intraocular pressure (IOP) in POAG is dueto progressive obstruction of drainage which may lead tothe damage of the optic nerve and subsequently blindness,if left untreated. Moreover, glaucoma and cataract incidenceincreasewith age and are frequently found in the same patient[2, 3]. Thus, cataract surgery may be a good managementoption in medically controlled nonsevere glaucoma with amild reduction in IOP [4, 5].

The iStent (Glaukos Corporation, Laguna Hills, CA) wasdeveloped to bypass the trabecular meshwork and create adirect route from the anterior chamber to Schlemm’s canal.

This ab interno device is implanted using the same temporalclear corneal incision used for cataract surgery.The iStent hasbeen shown to lower IOP while reducing ocular hypotensivemedication usage in prior studies involving eyes randomlyassigned to cataract surgery and iStent implantation orcataract surgery alone with follow-up through 1 year to24 months [6–9]. We reported in a previous study ourfindings involving subjects with POAG randomly assignedto phacoemulsification with micro-bypass stent implantationor phacoemulsification alone with a follow-up of 16 months[6]. IOP was statistically significantly lower in the combinedgroup both before and after washout as compared to thecontrol group. In addition, the mean number of medicationswas significantly lower in the combined group versus thecontrol group. The purpose of this recent work was to reporton long-term results through a minimum of 4 years on theoriginal cohort of subjects.

Hindawi Publishing CorporationJournal of OphthalmologyVolume 2015, Article ID 795357, 4 pageshttp://dx.doi.org/10.1155/2015/795357

2 Journal of Ophthalmology

2. Materials and Methods

2.1. Subjects and iStent. This prospective randomized studycomprised 36 subjects with cataract and POAG. Subjectswere required to have an IOP > 18mmHg in three differentvisits while using at least one ocular hypotensive medicationand a corrected distance visual acuity worse than 20/80.Key exclusion criteria were glaucoma other than POAG,cloudy cornea, potentially inhibiting gonioscopic view of theangle, peripheral anterior synechiae, prior ocular surgery,diabetic retinopathy, and age-related macular degeneration.Subjects were randomized in a 1 : 2 ratio to either iStentimplantation in conjunctionwith cataract surgery (combinedgroup) or cataract surgery alone (control group). The micro-bypass iStent (Glaukos Corporation, Laguna Hills, CA) isa heparin-coated L-shaped device (Duraflo, Edwards Life-sciences, Irvine, CA) made from titanium with a length of1.0mm and height of 0.33mm and snorkel with a diameterof approximately 120𝜇m. When implanted, the snorkel islocated in the anterior chamber and the open half-pipe lumen(foot) is located in Schlemm’s canal. This ab interno deviceestablishes a patent bypass through the trabecular meshworkto Schlemm’s canal to restore continuous physiologic outflow.

2.2. Surgical Technique. All subjects underwent standardclear corneal phacoemulsification with IOL implantation [6].All preoperative peribulbar anesthesia dosing was consideredcurrent standard of care. Subjects implanted with the iStent(combined group) underwent stent implantation after IOLimplantation.The stent was guided into the canal of Schlemmby ab interno gonioscopy using a Swan-Jacobs gonioscope.If no complications occurred during phacoemulsification,acetylcholine was injected into the anterior chamber afterIOL implantation to constrict the pupil.The anterior chamberwas then filled with an ophthalmic viscosurgical device toreform the anterior chamber and provide more clearance inthe angle. With the stent on the tip of the applicator, theanterior chamber was traversed with the applicator and thetrabecular meshwork located. The leading edge of the stentwas gently slid through the trabecular meshwork and into thecanal of Schlemm at the nasal position (3 to 4 o’clock in righteye; 9 to 8 o’clock in left eye) with the tip of the stent directedinferiorly. If there was difficulty with insertion at the primarylocation, a location of approximately 0.5 o’clock inferiorly wasattempted and the surgeon continued to move inferiorly asneeded for subsequent attempts. Next, the stent was releasedby pushing the button on the applicator. After the position ofthe stent was verified, the applicator was withdrawn.

2.3. Postoperative Follow-Up. Following the postoperativecourse described in the original paper, subjects were con-tacted again after approximately 4 years to determine theiravailability and willingness to undergo participation in afollow-up evaluation [6]. A total of 24 subjects agreed toparticipate. Subjects underwent an initial long-term eval-uation, at which time they were instructed to discontinueocular hypotensive medication and return 1 month later foran unmedicated assessment (washout evaluation).

2.4. Statistical Analysis. The efficacy analysis comprises allavailable long-term data on medicated IOP, ocular hypoten-sive medication use, and postmedication washout IOP. Forcontinuous variables, 2-sample 𝑡-tests were used to assessbetween-group differences. Fisher exact tests were used tocompare categorical outcomes between groups. An 𝛼 level of0,05was considered statistically significant. All statistical testswere performed using PC-SAS (Version 9.1.3).

3. Results and Discussion

3.1. Patients Demographics. Of the original cohort of 36randomized subjects, 24 subjects were available for long-termfollow-up assessment. A total of 5 subjects died, 5 subjectswere lost to follow-up, one subject refused washout, and onesubject could not travel to the clinic (Figure 1).

3.2. Intraocular Pressure. At baseline, mean IOP was 17,8 ±2,7mmHg in the combined group and 16,7 ± 3mmHg in thecontrol group (Table 1).

This difference was not statistically significant (𝑝 = NS).At the month 12 visit after washout, mean IOP was 16,1 ±2mmHg and 18,4 ± 3,1mmHg in the iStent and the controlgroup, respectively, a difference that was statistically signif-icant (𝑝 = 0,05). Long-term follow-up visit before washoutreported a mean IOP of 15,9 ± 2,3mmHg in the iStent groupand 17 ± 2,5mmHg in the control group (𝑝 = NS). Afterthe washout the IOP was 17,5 ± 2,3mmHg in the combinedgroup versus 20,4 ± 3,2mmHg in the control group. Inthe combined group we found no statistically significantdifference between before and after washout (𝑝 = 0,14) whileit was found in the control group (𝑝 = 0.04). At the long-termfollow-up visit after washout we found a difference of 14,2%between groups formean IOP reduction (𝑝=0,02) (Figure 2).The difference between baseline and after washout IOP was0,3mmHg in the combined group versus 3,7mmHg in thecontrol group.

3.3. Ocular Hypotensive Medications. At baseline, the meannumber of ocular hypotensive medications used was 1,9 ± 0,9in the combined group and 1,8 ± 0,7 in the control group, adifference that was not statistically significant (𝑝 = NS). At 12months, themean number ofmedications was 0,4 ± 0,7 in thetreatment group and 1 ± 1 in the control group (Table 2).

These reductions were statistically significant comparedto baseline values (𝑝 = 0,003 for treatment group and 𝑝 = 0,01for the control group).

At long-term follow-up patients in the combined groupused 0,5 ± 0,8 medications, a difference statistically signifi-cant compared to baseline (𝑝 = 0,005). Patients in the controlgroup also had a significant reduction in the mean numberof ocular hypotensive medications used (0,9 ± 1 medications;𝑝 = 0,01). No statistically significant difference was reportedbetween groups at any visit.

3.4. Safety. The majority of patients had an improvement ofUDVA and CDVA after phacoemulsification and intraocularlens (IOL) implantation. No significant differences were

Journal of Ophthalmology 3

Total36 eyes

Combined group(stent + phacoemulsification)

12 eyes

n = 1 lost to follow-upn = 1 refused washout

Long-term data10 eyes

Control groupPhacoemulsification

24 eyes

n = 5 diedn = 4 lost to follow-upn = 1 unable to visit the clinic

Long-term data14 eyes

Figure 1: Subject accountability: a total of 10 eyes in the combined group and 14 eyes in the control group had long-term follow-up data.

Table 1: Mean IOP values (mmHg) by visit.

Baseline 12 months 12 months wo. 48 months 48 months wo.Treatment group (SD) 17,8 (2,7) 14,7 (1,3) 16,1 (2) 15,9 (2,3) 17,5 (2,3)Control group (SD) 16,7 (3) 15,6 (1,1) 18,4 (3,1) 17 (2,5) 20,4 (3,2)SD: standard deviation; wo.: washout.

15,917

IOP prior to washout IOP after washout

Combined groupControl group

0

5

10

15

20

25

Mea

n IO

P (m

mH

g)

20,4∘

17,5∗

∘p value = 0,04∗p value = 0,14

Figure 2: Mean intraocular pressure (IOP) at long-term follow-upbefore and after washout of ocular hypotensive medications at long-term follow-up (𝑝 values prior to and after washout: 0,14 in thecombined group and 0,04 in the control group).

Table 2: Ocular hypotensive medications by visit (mean values).

Baseline 12 months 48 monthsTreatment group (SD) 1,9 (0,9) 0,4 (0,7) 0,5 (0,8)Control group (SD) 1,8 (0,7) 1 (1) 0,9 (1)SD: standard deviation.

reported between groups at 12- and 48-month follow-up.No postoperative stent-related adverse events were observedin these eyes through 48 months. IOP was well controlledin both groups throughout the entire follow-up period; nosecondary surgical intervention was required to control IOP.

In this study, the implantation of the iStent combinedwithcataract surgery resulted in a greater IOP reduction at long-term follow-up compared to cataract surgery alone. Ocularhypotensive medications used were reduced, both in thecombined and in the control group. The micro-bypass stentcombined with phacoemulsification constantly reduced IOPthroughout the entire study, starting from 17,8 ± 2,7mmHg atbaseline to 16,1 ± 2mmHg at 12 months and finally to 15,9 ±2,3mmHg at 48 months. Mean IOP in patients with cataractand POAG treated with phacoemulsification alone, increasedat follow-up visits after washout. At long-term follow-up afterwashout, IOP in the control group was significantly greaterthan at baseline (20,4 ± 3,2mmHg versus 16,7 ± 3mmHg, 𝑝= 0,002) and a 14,2% difference compared to the combinedgroup was reported, which was statistically significant (17,5 ±2,3mmHg in the combined group versus 20,4 ± 3,2mmHg inthe control group, 𝑝 = 0,02). The results show how the iStentimplantation combined with cataract surgery maintains itsefficacy in lowering IOP in the long term, as reported inprevious studies [6–9].Mean IOP in the control group tendedto rise at 48-month follow-up in our study.This data suggestsa loss of efficacy with time for phacoemulsification alone,as previously reported in other studies [6–10]. The decreasein the number of glaucoma medications in our study issimilar in both groups (1,4 ± 0,8 the difference observed inthe combined group versus 0,9 ± 1 in the control group).A similar reduction is observed in other studies [6, 8, 10].The reduction in the number of medications for chronicuse in POAG remains a fundamental question with a viewto improve patients compliance and to reduce conjunctivalinflammation, preserve patients ocular surface integrity, andprevent from reduction in the success rate of subsequenttrabeculectomy [11, 12]. With regard to safety, no adverseevents related to the stent implantation were observed.

4 Journal of Ophthalmology

4. Conclusions

There are a number of strengths in this study. The length ofits follow-up is certainly one of them, being one of the longestto be reported in literature to our knowledge [10]. More-over, the patients’ cohort included in the study presentedwith an increasingly common situation—primary open-angleglaucoma—encountered concomitantly with cataract. Ourresults are a measure of effectiveness more than a measureof efficacy.

Our study is not without limitations. After the first 12months patientswere referred back to their ophthalmologists,so IOP lowering medications were not prescribed based on astandardized protocol.This biasmight be a reason for the lackof statistical significance in themean number of medications.This is also why the results obtained after washout should beconsidered more significant. Finally, the number of patientsevaluated at follow-upwas small, with 10 eyes in the treatmentgroup and 14 eyes in the control group. Our results needconfirmation in larger randomized controlled clinical trials.

In conclusion, patients having a combined cataractsurgery with iStent implantation maintained low IOP levelsafter 48 months of follow-up. Cataract surgery alone showeda loss of efficacy in controlling IOPover time. Both treatmentsreduced the number of ocular hypotensive medicationsprescribed.

Ethical Approval

Statement of human rights: all procedures performed in thisstudy involving humans were in accordance with the ethicalstandards of the institutional committee and with the 1964HelsinkiDeclaration and its later amendments or comparableethical standards.

Consent

Informed consent was obtained from all individual partici-pants included in this study.

Conflict of Interests

The authors declare that they have no conflict of interests.

References

[1] C. Cedrone, R. Mancino, F. Ricci, A. Cerulli, F. Culasso, andC. Nucci, “The 12-year incidence of glaucoma and glaucoma-related visual field loss in Italy: the Ponza eye study,” Journal ofGlaucoma, vol. 21, no. 1, pp. 1–6, 2012.

[2] J. T. F. Lau, V. Lee, D. Fan, M. Lau, and J. Michon, “Knowledgeabout cataract, glaucoma, and age relatedmacular degenerationin the Hong Kong Chinese population,” British Journal ofOphthalmology, vol. 86, no. 10, pp. 1080–1084, 2002.

[3] D. S. Friedman, H. D. Jampel, L. H. Lubomski et al., “Surgicalstrategies for coexisting glaucoma and cataract: an evidence-based update,” Ophthalmology, vol. 109, no. 10, pp. 1902–1913,2002.

[4] B. J. Poley, R. L. Lindstrom, T. W. Samuelson, and R. Schulze Jr.,“Intraocular pressure reduction after phacoemulsification withintraocular lens implantation in glaucomatous and nonglauco-matous eyes. Evaluation of a causal relationship between thenatural lens and open-angle glaucoma,” Journal of Cataract andRefractive Surgery, vol. 35, no. 11, pp. 1946–1955, 2009.

[5] A. Shrivastava andK. Singh, “The effect of cataract extraction onintraocular pressure,” Current Opinion in Ophthalmology, vol.21, no. 2, pp. 118–122, 2010.

[6] A. M. Fea, “Phacoemulsification versus phacoemulsificationwith micro-bypass stent implantation in primary open-angleglaucoma,” Journal of Cataract and Refractive Surgery, vol. 36,no. 3, pp. 407–412, 2010.

[7] T. W. Samuelson, L. J. Katz, J. M. Wells, Y.-J. Duh, and J.E. Giamporcaro, “Randomized evaluation of the trabecularmicro-bypass stent with phacoemulsification in patients withglaucoma and cataract,”Ophthalmology, vol. 118, no. 3, pp. 459–467, 2011.

[8] D. Spiegel, J. Garcia-Feijoo, and M. Martinez de la Casa, “iStenttrabecular micro-bypass and concurrent cataract surgery: 24month results,” in Proceedings of the Annual Meeting of theAssociation for Research in Vision and Ophthalmology (ARVO’09), Fort Lauderdale, Fla, USA, May 2009.

[9] E. R. Craven, “Prospective randomized controlled trial ofcataract surgery with trabecular micro-bypass stent in mild-moderate open angle glaucoma: safety in two-year follow-up,” in Proceedings of the American Society for Cataract andRefractive SurgeryAnnualMeeting (ASCRS ’11), SanDiego, Calif,USA, March 2011.

[10] P. Arriola-Villalobos, J. M. Martinez-de-la-Casa, D. Dıaz-Valle,C. Fernandez-Perez, J. Garcia-Sanchez, and J. Garcia-Feijoo,“Combined iStent trabecular micro-bypass stent implantationand phacoemulsification for coexistent open-angle glaucomaand cataract: a long-term study,” British Journal of Ophthalmol-ogy, vol. 96, no. 5, pp. 645–649, 2012.

[11] R. J. Noecker, L. A. Herrygers, and R. Anwaruddin, “Cornealand conjunctival changes caused by commonly used glaucomamedications,” Cornea, vol. 23, no. 5, pp. 490–496, 2004.

[12] D. C. Broadway, I. Grierson, C. O’Brien, and R. A. Hitchings,“Adverse effects of topical antiglaucoma medication. The out-come of filtration surgery,” Archives of Ophthalmology, vol. 112,no. 11, pp. 1446–1454, 1994.

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Clinical Study Micro-Bypass Implantation for Primary Open ...downloads.hindawi.com/journals/joph/2015/795357.pdf · Purpose . To report the long-term follow-up results in patients